Applications of parallel synthetic lead hopping and pharmacophore-based virtual screening in the discovery of efficient glycine receptor potentiators.
Eur J Med Chem
; 137: 63-75, 2017 Sep 08.
Article
em En
| MEDLINE
| ID: mdl-28575722
ABSTRACT
Glycine receptors (GlyRs) are pentameric glycine-gated chloride ion channels that are enriched in the brainstem and spinal cord where they have been demonstrated to play a role in central nervous system (CNS) inhibition. Herein we describe two novel classes of glycine receptor potentiators that have been developed using similarity- and property-guided scaffold hopping enabled by parallel synthesis and pharmacophore-based virtual screening strategies. This effort resulted in the identification of novel, efficient and modular leads having favorable in vitro ADME profiles and high CNS multi-parameter optimization (MPO) scores, exemplified by azetidine sulfonamide 19 and aminothiazole sulfone (ent2)-20.
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MEDLINE
Assunto principal:
Sulfonamidas
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Receptores de Glicina
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Descoberta de Drogas
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article